Simulated Microgravity-Induced Epigenetic Changes in Human Lymphocytes
Simulated Microgravity-Induced Epigenetic Changes in Human Lymphocytes
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DOI：
10.1002/jcb.22674
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发表时间：
2010-09-01
影响因子：
4
通讯作者：
DuMond, James W.
中科院分区：
文献类型：
--
作者：
Singh, Kamaleshwar P.;Kumari, Ragini;DuMond, James W.
真实的太空飞行和模拟的微重力条件导致控制重要细胞功能的基因表达的变化。微重力诱导的基因表达变化的机制尚不清楚。已知DNA甲基化和染色质肿瘤修饰的表观遗传学变化调节基因表达。本研究的目的是研究模拟微重力是否改变（a）DNA甲基化和组蛋白乙酰化，以及（B）DNMT 1、DNMT 3 a、DNMT 3 B，为了实现这些目标，人T淋巴细胞在模拟微重力的旋转细胞培养系统（RCCS）转盘中生长。用甲基化敏感随机扩增多态性DNA（methylation sensitive-random amplified polymorphic DNA，MS-RAPD）分析仪检测微重力诱导的DNA甲基化变化。实时荧光定量PCR检测基因表达。DNMT 1、DNMT 3a和DNMT 3b的表达在微重力暴露72 h时升高，7 d时降低。MS-RAPD分析显示，模拟微重力暴露导致DNA低甲基化和突变变化。HDAC 1表达的降低应导致乙酰化历史H3水平的增加，然而在微重力条件下观察到乙酰化H3水平的降低，从而表明其他HDACs可能参与H3去乙酰化的调节。因此，研究结果表明，表观遗传事件可能是微重力诱导的基因表达变化和相关不良健康影响的机制基础之一。生物化学111 123-129。2010（C）2010 Wiley-Liss。Inc
Real space flight and modeled microgravity conditions result in changes in the expression of genes that control important cellular functions However. the mechanisms for microgravity-induced gene expression changes are not clear The epigenetic changes of DNA methylation and chromatin tummies modifications are known to regulate gene expression The objectives of this study wine to investigate whether simulated microgravity alters (a) the DNA methylation and histone acetylation, and (b) the expression of DNMT1 DNMT3a, DNMT3b, and HDAC I genes that regulate epigenetic events To achieve these objectives, human T-lymphocyte cells were grown in a rotary cell culture system (RCCS) dial simulates microgravity. and in parallel under normal gravitational conditions as control The microgravity-induced DNA methylation changes were detected by methylation sensitive-random amplified polymorphic DNA (MS-RAPD) analysts of genomic DNA. The gene expression was measured by Quantitative Real-time PCR The expression of DNMT1, DNMT3a, and DNMT3b was found to be increased at 72 h and decreased at 7 days in microgravity exposed cells The MS-RAPD analysis revealed that simulated microgravity exposure results in DNA hypomethylation and mutational changes Gene expression analysis revealed microgravity exposure tune-dependent decreased expression of HDAC1. Decreased expression of HDAC1 should result in increased level of acetylated historic H3, however a decreased level of acetylated H3 was observed in microgravity condition, indicating thereby that other HDACs may be involved in regulation of H3 deacetylation The findings of thus study suggest that epigenetic events could be one of the mechanistic bases for microgravity-induced gene expression changes and associated adverse health effects J Cell. Biochem. 111 123-129. 2010 (C) 2010 Wiley-Liss. Inc